Anticoagulants and Antiplatelet Drugs Flashcards
Factor IIa Inhibitors
Unfractionated Heparin*
Dabigatran
Fondaparinux
Heparin Site of Action
Combines with antithrombin III (ATIII) to inactivate active clotting factors (IIa, IXa, Xa, XIa, XIIa)
LMWHs/ Fondaparinux Site of Action
Combine with antithrombin III (ATIII) to inactivate Xa
Hirudin, Dabigatran Site of Action
Directly inactivate IIa (thrombin)
Rivaroxaban Site of Action
Directly inactivates Xa
Venous Thrombi Composition
Composed mainly of fibrin and trapped red blood cells with relatively few platelets
Atrial Thrombi Composition
Composed mainly of platelet aggregates held together by small amounts of fibrin
Anticoagulant Agent Uses
Drugs of choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic events in patients with atrial fibrillation. Anticoagulants are also effective for arterial thrombosis and their effects can be additive with antiplatelet agents
Antiplatelet Agent Uses
Drugs of choice primarily for prevention and treatment of arterial thrombosis (primary and secondary prevention and treatment of acute coronary syndrome).
Primary Prevention of ACS
W/ Risk Factors: Use Aspririn
W/O Risk Factors: Apsirin for Men >45 and women above >65
Secondary Prevention
Recent MI → Aspirin (clopidogrel if aspirin intolerant)
Ischemic Stroke → Aspirin + clopidogrel
UA/NSTEMI Treatment
Asprin
± clopidogrel
± UFH, LMWH or fondaparinux
± GPIIb/IIIa inhibitor
Acute MI (STEMI) Treatment
Aspirin + clopidogrel
+ UFH, LMWH or fondaparinux
+ GPIIb/IIIa inhibitor
PCI Treatment
Aspirin + clopidogrel
+ UFH, LMWH or fondaparinux
+ GPIIb/IIIa inhibitor
AFib Treatment
Warfarin or dabigatran or rivaroxaban or apixaban
(aspirin can be used for patients at low risk)
Venous Thromboembolism (VTE) Treatment
LMWH or UFH or
fondaparinux + warfarin
VTE Prevention
1) Hospitalized/Gen Surgery - Low-dose UFH or LMWH or fondaparinux
2) Ortho Surgery - Fondaparinux or rivaroxaban or dabigatran or LMWH or warfarin
PAD Treatment
Aspirin (clopidogrel if aspirin intolerant)
aPTT is used to monitor?
Heparin therapy (not significantly affected by LMWHs)
Heparin Mechanism
Binds to Antithrombin III (AT III) and increases its activity 1000 fold. Inhibits factors 2, 9, 10, 11, 12 and 13.
LMWH (Enoxapirin) and Fondaparinux Mechanisms
- Bind to AT III and inactivate factor Xa, but not IIa (thrombin)
- Claimed to have equal efficacy as regular heparin for VTE with less tendency for bleeding complications and less effects on platelets (i.e.,thrombocytopenia)
Direct Thrombin IIa Inhibitors
Argatroban, bivalirudin, lepirudin, desirudin- all given parenterally
Heparin & Derivative Pharmacokinetics
Not absorbed in GI Tract
Given Paranterally w/ IV Loading dose
Drug of choice if pregnant
FIRST ORDER RENAL ELIMINATION!!
LMWH vs Heparin
LMWH Generally preferred due to less variable response (no monitoring needed) and less thrombocytopenia
Adjunct treatment in unstable angina/ acute MI
Heparin/ Derivatives Adverse Rxns
Hemorrhage is the chief complication
Hypersensitivity
Thrombocytopenia
Osteoporosis
Heparin & LMWH Overdosage Sign and Treatment
Bleeding is the chief sign
GIVE PROTAMINE!!
Warfarin Mechanism
Acts in liver to prevent synthesis of clotting factors. Does not work until clotting factors are turned over.
Warfarin Targets
Vitamin K-dependent clotting factors (II, VII, IX, X and Ca2+ dependent factors)
Warfarin Uses
AFib
Prophylaxis/ treatment of thromboembolism
Warfarin Adverse Rxns
Hemorrhage Necrosis of fatty soft tissue (use heparin bridge) GI Issues Osteoporosis DON'T USE IF PREGNANT!
Warfarin Overdose Signs and Treatments
Signs: Hematuria, excessive menorrhagia, gum bleeding
Major Bleeding- Hold warfarin, administer 5-10 mg of Vitamin K IV. Also use Prothrombin complex concentrate (PCC)
Dabigatran Mechanism
Acts in the plasma to directly inhibit the activity of thrombin (Factor IIa). Does NOT require frequent monitoring and dosage adjustments. NO ANTIDOTE!
Dabigatran Pharmacokinetic
Absorbed as a prodrug (etexilate) and converted to active form by plasma and liver esterases. Excreted renally.
Dabigatran Uses
AFib!
Dabigatran Adverse Rxns
Bleeding in 17% of pt’s (3% w/ major bleeding event)
GI Complaints
Fewer DDI than warfarin
Anticoagulant effect is IRREVERSIBLE!
Antiplatelet Agents
Aspirin
Clopidogrel
Dipyridamole
Abciximab/ Eptifibatide/ Tirofiban
Aspirin Mechanism
Small dose (40-80 mg) inhibits COX-1 synthesis of thromboxane in platelets. Largest [acetylsalicyclic acid] is in the portal vein so highest effect on circulating COX-1 (not tissue COX-2)
Clopidogrel Mechanism
ADP (purinergic-P2Y12) receptor antagonists that interfere with ADP-induced platelet aggregation. Clopidogrel is prodrug converted to active metabolite by CYP450, which then irreversibly inhibits receptor.
Dipyridamole Mechanism
Blocks phosphodiesterase breakdown of cAMP, elevating cAMP levels and potentiating prostacyclin’s anti-aggregatory action. Combined with aspirin as Aggrenox. Little or no apparent benefit as antithrombotic agent.
Abciximab/Eptifibatide/Tirofiban Mechanism
Blocks IIb/IIIa receptors on platelet thus preventing integrin and fibrinogen binding that facilitates aggregation (platelet-platelet binding). Advantage of blocking all pathways of platelet activation.
What antiplatelet agent(s) is/are dosed intravenously?
Abciximab, Eptifibatide, Tirofiban
Clopidogrel Adverse Rxns
GI upset, headache, dizziness, upper respiratory infection, bleeding; concomitant use of proton pump inhibitors (PPIs) may inhibit activation of clopidogrel by CYP2C19
Prasugrel and Ticagrelor Adverse Rxns
Bleeding!
GIIb/IIIa inhibitor Adverse Rxns
Bleeding!
Acute MI Anti-platelet drugs
Aspirin (chewed and swallowed) plus ADP antagonist
Unstable Angina Anti-platelet drugs
Aspirin ± ADP antagonist
Percutaneous Coronary Interventions (PCI) Anti-platelet drugs
Aspirin plus ADP antagonists ± GIIb/IIIa inhibitors
Secondary Prevention of Acute MI Anti-platelet Drugs
Aspirin!
Secondary Prevention of Ischemic Stroke Anti-platelet Drugs
Aspirin ± dipyridamole
Anticoagulants we need to know
Heparin (UFH) / enoxaparin (LMWH), warfarin, dabigatran, rivaroxaban
Antiplatelet agents we need to know
Aspirin, clopidrogel, GIIB/IIIa inhibitors (as class: abciximab / eptifibatide / tirofiban)
Thrombolytic Agents we need to know
Tissue Plasminogen Activator (tPA) and variants